Human gene changes how mice squeak

Human DNA inserted into mice caused their offspring to squeak at a different pitch, suggesting that the gene involved may be linked to people's ability to speak.

The gene, FOXP2, was identified in 1998 as the cause of a subtle speech defect in a large London family, half of whose members have difficulties with articulation and grammar. All those affected inherited a disrupted version of the gene from one parent.

The gene quickly attracted the attention of evolutionary biologists because the human version of FOXP2 differs significantly in its DNA sequence from those of mice and chimpanzees.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, genetically engineered a strain of mice whose FOXP2 gene has been swapped out for the human version.

The study was the first to explore the effect of modifying genes in an animal and the relevance to human evolution, the authors said. The researchers said they used mice because it would be impossible or unethical to genetically manipulate chimps or humans, and mice are the only mammal that can easily have genes modified and the effects measured.

The findings are reported in the current issue of the journal Cell by Wolfgang Enard, also of the Leipzig institute, and a team of German researchers who studied 300 features of the humanized mice.

Svante Paabo, in whose laboratory the mouse was engineered, promised several years ago that when the project was completed, “We will speak to the mouse.” He did not promise that the mouse would say anything in reply.

Baby mice utter ultrasonic whistles when removed from their mothers. The humanized baby mice, when isolated, made whistles that had a slightly lower pitch, among other differences, Enard said. Enard argued that putting significant human genes into mice is the only feasible way of exploring the essential differences between people and chimps, our closest living relatives.

“One possibility is that the amino acid substitutions in FOXP2 contributed to an increased fine-tuning of motor control necessary for articulation, i.e., the unique human capacity to learn and coordinate the muscle movements in lungs, larynx, tongue and lips that are necessary for speech,” the researchers wrote.

FOXP2, a gene whose protein product switches on other genes, is important during the embryo's development and plays an active part in constructing many tissues, including the lungs, stomach and brain. The gene is so vital that mice in which both copies of the gene are disrupted die after a few weeks.